Minaj, 36, performed their collaboration Side to Side as well as Bang Bang, which also features Jessie J, as Grande closed the first weekend of the annual festival.
But Minaj could barely be heard in parts and kept touching her ear piece after being blighted by technical issues.
Grande appeared to shout “we can't hear anything” as Minaj struggled to get through her rap midway through Bang Bang. The performance was deemed a “mess” by fans watching on the live stream who begged organisers to find her a new microphone.
“Nicki Minaj did not deserve that at all, I'm actually so annoyed, so painful to watch especially when it's something out of her control #Coachella,” wrote one Twitter user.
Another posted: “Who do I have to fight at #coachella for sabotaging the queen of rap, nicki minaj? I want to fist fight for thirty minutes. Period. I’ll be waiting for you AT THE DOOR #coachella2019.”
Coachella did Nicki Minaj so dirty omg— brietta (@Bites_)April 15, 2019
— Michael (@michaelcollado)April 15, 2019
it’s only me or nicki's microphone isn't working? she looks uncomfortable— carla (@starkfantsy)April 15, 2019
they really playing with Nicki’s microphone you can’t hear the girlie at all— katie (@biebersantics)April 15, 2019
— eBby (@1800EHO)April 15, 2019
Someone get nicki a new microphone i-— m. (@ghostinmutual)April 15, 2019
either nicki’s microphone is broken or the instrumental is too loud,,,,, someone’s getting fired sksks,,,— 𝖍𝖊𝖑𝖊𝖓𝖆 (@eriovixia)April 15, 2019
Others joked that Minaj’s longtime rival Cardi B had “sabotaged” her big moment.
Grande’s set saw her storm through a string of her biggest hits including God is a Woman, NASA and Thank U, Next which wrapped up with a firework display.
P Diddy and Ma$e joined her on stage after NSYNC to perform Mo Money Mo Problems. They also appeared to struggle with sound issues with fans calling for the sound team to be “sacked”.
One tweeted: “MA$E a real one, because the engineers are clearly out to get the rappers tonight. He fought through it #ARICHELLA.”
Another wrote: “@Diddy and #mase 's mics weren't the best either now that I'm reflecting. What happened sound engineer? Do you only like @ArianaGrande and @NSYNC? #ARICHELLA.”
Diddy paid tribute to Grande who recently revealed she is suffering from PTSD in the wake of the Manchester Arena attack at her concert in 2017 and the death of her ex-boyfriend Mac Miller last year.
“My sister here been through a whole lot and she’s still standing and she’s with you,” Diddy told the crowd. “Give it up for the number one artist!”
Kanye West and Childish Gambino are among those performing next weekend.