The poet-prophet opened the Chicago stop of his 42-date Homeward Bound farewell tour with the melancholy "America," an epic folk anthem that many Baby Boomers in the audience first heard on the 1968 Simon & Garfunkel album Bookends.

More than 17,000 concert-goers gathered last night at the aptly named United Center to hear legendary musician Paul Simon present his classic songs and eclectic sounds.

But whether they were introduced to Mr. Simon's ubiquitous music on an LP or an elevator, the whole, happy throng sang, danced, clapped, and cried throughout the dazzling 26-song set that featured American standards as well as deep-catalogue gems.

Younger people in the crowd recognized it as the campaign song for U.S. Senator Bernie Sanders of Vermont when he ran for president in 2016.

The second song performed was the 1975 chart-topper, "50 Ways to Leave Your Lover," opening with Jim Oblon's military drum riff, followed by Mr. Simon's smooth, Sinatra-style lyrics.

"I would say this is my favorite city, but I'm not contractually allowed to say that," he quipped to his Windy City fans, who cheered enthusiastically. "But it's true."

'"The problem is all inside your head,' she said to me/'The answer is easy if you take it logically."'

And when the tune shifted gears into its funky romp, much of the United Center crowd was on their feet, singing along and perhaps recalling how they were once inspired to exit a toxic relationship.

A virtuoso guitar player himself, Mr. Simon was accompanied by a nine-member, multi-instrumental ensemble, plus the chamber-music sextet yMusic, which National Public Radio has ordained the "future of classical music."

"You just slip out the back, Jack/Make a new plan, Stan/Don't need to be coy, Roy, just listen to me/Hop on the bus, Gus, don't need to discuss much/Just drop off the key, Lee, and get yourself free."

Led by Rhymin' Simon, the big-sounding band took the audience on an "It's a Small World" cultural ride that spanned the globe of musical genres.

There was the Jamaican reggae of Mr. Simon's 1971 hit "Mother and Child Reunion," the Brazilian samba of 1972's "Me and Julio Down by the Schoolyard," the African pop/chant of 1986's "Diamonds on the Soles of Her Shoes," and the catchy electronic funk of "Wristband" from his latest studio album, 2016's Stranger to Stranger.

For many of us, the sounds of Simon were indeed the soundtrack of our lives. He is arguably the greatest singer/songwriter of his generation. While not as influential as Bob Dylan, his music was more accessible to the masses. And in the late 1960s, Simon and his singing partner Art Garfunkel sold more records than a little band called The Beatles.

For the record, Mr. Simon has earned sixteen Grammy awards, is a member of the Rock and Roll Hall of Fame, and was the first recipient of the Library of Congress's Gershwin Award for Popular Song.

While ever expanding the horizons of his artistic vision, the five-foot-three music giant went truly global in 1985 when he traveled to apartheid South Africa, breaking the performers boycott of that country, collaborating with accomplished local musicians, and producing his masterwork Graceland, which won Grammy Album of the Year honors.

The mega-hit from that game-changing album, "You Can Call Me Al," was the showstopper of the Chicago concert. Mr. Simon jokingly calls the song the national anthem "because everyone stands up for it." The United Center crowd was no exception, aided in their joyful singing by a jumbo backdrop screen that featured flashes of the song's colorful lyrics.

"I need a photo opportunity/I want a shot of redemption/Don't want to end up a cartoon/In a cartoon graveyard."

If you really want to see how music can demolish barriers of class and color, watch the YouTube video of Mr. Simon singing "You Can Call Me Al" in 1987 at a sold-out soccer stadium in Zimbabwe, Africa, where blacks and whites danced jubilantly together.

More than thirty years later, he is still bringing people together. The Homeward Bound tour heads to Europe later this month, and then returns to the states in the fall for three shows at Madison Square Garden and a to-be-announced location in New York City.

The music world is swirling with rumors that Mr. Simon will again stage a free concert in Central Park, as he did with Mr. Garfunkel in 1981, and as a solo act in 1991, performing before a total of a million people––maybe more.

On this final tour, he is pointedly not singing his magnum opus, "Bridge Over Troubled Waters." Perhaps he is saving the high-pitched hymn for his childhood chum "Artie" in a surprise appearance?

I am skeptical about "farewell tours," having attended The Who's allegedly last concert, at the Los Angeles Coliseum––in 1982.

Addressing the question of whether he was really retiring, Mr. Simon was not coy, Roy.

"I'm going to continue writing music," he assured his loyal fans, who responded with hearty applause.

At 76, Mr. Simon's voice is rustproof. And his fingers still fly up and down the fret of his guitar. He even danced during the opening accordion of the zydeco-tinged "She Was Your Mother."

Moreover, he is still reinventing his music, modulating keys, changing phrasings, and graciously cuing his fellow musicians when it's their time to shine. One of the many band standouts last night was Andy Snitzer's heavenly sax solo on the jazzy "Still Crazy After All These Years," the title track from Mr. Simon's 1975 Grammy Album of the Year.

The youthful members of yMusic encircled the cerebral singer during the 1990 tune "Can't Run But," immaculately playing, respectively––the violin, viola, cello, flute, clarinet and trumpet.

The sextet also created the mood and movement for "René and Georgette Magritte with Their Dog After the War," a surreal 1983 song that Mr. Simon explained was inspired by a book that he randomly picked up at Joan Baez' house while visiting the famed folksinger.

Also starring during the two-and-a-half-hour concert were keyboard wizard Mick Rossi as well as gifted guitarists Mark Stewart and Bakithi Kumalo, he of the iconic slap-bass run on "You Can Call Me Al." Mr. Simon's other longtime guitar player, Vincent Nguini, died last December, one of the reasons the performer has given for his decision to stop touring.

Mr. Nguini's replacement, Biodun Kuti, was equally stellar, especially on "Spirit Voices" and "The Obvious Child," both tracks from The Rhythm of the Saints, Mr. Simon's blockbuster 1990 follow-up to Graceland.

A harbinger of the singer's post-touring career may have been when he performed the environmentally conscious "Questions for the Angels" from the critically acclaimed 2011 album So Beautiful So What. It is easy to envision the longtime philanthropist playing benefit concerts on behalf of saving the planet and other peaceful causes.

The first of three encore sets was kicked off by the title track from Graceland, a Sun Records-rooted song that brilliantly describes a rite-of-passage pilgrimage to the Elvis Presley mansion-museum.

"The Mississippi Delta was shining/Like a national guitar/I am following the river/Down the highway/Through the cradle of the Civil War/I'm going to Graceland."

Then there was the irresistible 1973 hit "Kodachrome," which includes one of the most clever and clairvoyant lines ever written.

"And though my lack of education hasn't hurt me none/I can read the writing on the wall."

Nearly a half century ago, Mr. Simon wrote prophetically, "Still a man hears what he wants to hear and disregards the rest," predicting our present dark age of alternative facts and fake news.

The hallowed song from which those perspicacious lyrics came, "The Boxer," was perfected in the second encore session by Mr. Simon's wistful voice and finger-picking guitar mastery––plus, a freight-train rhythm, crashing cymbals, and solemn trumpet solo by yMusic's C.J. Camerieri.

It is still an astonishing song, with multi-layered lyrics that change narratives from a youth's leaving-home lament to a third-person portrait of a battered prizefighter.

"In the clearing stands a boxer/And a fighter by his trade/And he carries the reminders/Of ev'ry glove that laid him down/Or cut him till he cried out/In his anger and his shame/'I am leaving, I am leaving'/But the fighter still remains."

Mr. Simon joyously and generously shared the plaintive hook with the animated, emotional crowd.

"Lie la lie, lie la la la lie lie/Lie la lie, lie la la la la lie la la lie."

The 1966 ballad "Homeward Bound" off the album Parsley, Sage, Rosemary, and Thyme was made particularly poignant by a slideshow that traced Mr. Simon's journey from "a poet and a one-man band" to a world-renowned composer for the ages.

Finally, the fitting last encore was "The Sound of Silence," the 1965 breakthrough single that propelled the voices of Simon & Garfunkel into the collective neurons of the nation's consciousness.

Alone in the spotlight with his acoustic guitar, Paul gave his all, singing the timeless lyrics passionately and powerfully.

"Hello darkness, my old friend/I've come to talk with you again/Because a vision softly creeping/Left its seeds while I was sleeping/And the vision that was planted in my brain/Still remains/Within the sound of silence."

The transcendent song was a soft exclamation point to an almost spiritual night. The audience cheered and clapped for more than two minutes, as Mr. Simon clasped his hands together in a prayer-like expression of gratitude.

All of this was apropos for a musician whose songs have always been replete with religious references:

"Jesus loves you more than you will know" from "Mrs. Robinson"; "These are the days of miracles and wonders" from "The Boy in the Bubble"; and "He sees angels in the architecture/Spinning in infinity/He says, 'Amen' and 'Hallelujah!'" from "You Can Call Me Al."

So whether we are blessed to hear Paul Simon sing again here on earth––or in the hereafter––his vision will remain.