Etheridge pulled out a musical arsenal, playing several guitars, harmonica, drums and keyboards.

Singer-songwriter Melissa Etheridge was midstream into a stripped down acoustic version of her stinging rocker “All American Girl” at Centennial Hall Saturday night when she stopped singing.

She strummed her acoustic guitar and looked out into the audience.

“I met a woman tonight,” she said in her trademark raspy voice, and the crowd of 2,000 — mostly women — cheered. “I met a woman named Gabbie Giffords. You talk about an all-American girl.”

The audience rose to its feet and turned toward Gabrielle Giffords, the former Tucson congresswoman who was sitting about a dozen rows from the stage surrounded by her husband, Mark Kelly, and former aid-turned-Congressman Ron Barber. The applause was deafening as Giffords, the victim of the Jan. 8 mass shooting in Tucson, raised her hand to acknowledge the attention.

Etheridge’s fans were still applauding when she lit into the driving final stanza, performing it with the blazing energy and tempo that made it one of the singer’s most enduring female-empowering anthems.

Saturday’s concert was Etheridge’s first here in 21 years. In 1992, she played a sold-out show at Tucson Music Hall and had intended to return in 2004, but canceled after being diagnosed with breast cancer.

“It’s been a long time, Tucson,” Etheridge told the audience, which didn’t quite fill out Centennial Hall to open the 2013-14 UApresents season. “We have so much catching up to do. So much to tell you.”

Her show traversed her 25-year career. She pulled gems from her dozen career albums, going back to her early hits — “Brave and Crazy,” “Bring Me Some Water” and “I’m The Only One” — and bringing us up to date with “Shout Now,” “The Shadow Of A Black Crow” and the title song off her latest album “4th Street Feeling.”

But it was what she performed in between that was the true genius of her performance. She pulled deep album cuts including “Goodnight” off 2001’s “Skin” and “An Unexpected Rain” from 2007’s “The Awakening,” singing them with the intensity of those hits that made her a multiplatinum, Grammy-winning artist.

She played guitar on every song, taking the lead on acoustic and electric, and blasted away on harmonic to add a bluesy blister on “Shout Now.” She played keyboards on “4th Street Feeling” and a cover of Joan Armatrading’s heart-breaking “Weakness In Me.” She even banged on the drums with her drummer Blair Sinta.

We didn’t’ see this multi-instrumental side of her in 1992. We’ve missed a lot during her absence. The heavy heart that she could never quite mask back then is a memory. She still sings her female-empowering anthems with conviction, but she delivered her heart-breaking tales of unrequited or unfulfilled love — “Come To My Window” and “You Can Sleep While I Drive,” with its lyric about driving through Tucson — with a little less pain.

She is happier and healthier than she’s ever been, she told Saturday’s audience, then segued into “I Run For Life,” a song inspired by her cancer.