The SNP politician has said he is fed up with the daily “barrage” of abuse – some of which has been aimed at his newborn baby daughter.
Mr Yousaf was the first Holyrood minister to come from an ethnic minority background.
Last year, he revealed he fears for his life and carries a personal alarm following racist death threats and online abuse.
He was forced to step up security at his home and constituency office and no longer conducts surgeries alone following the threats.
The abuse has included a troll responding to a picture of him and his family with the message: “Yet another problem that a machine gun would solve.”
Announcing his decision to quit Twitter, Mr Yousaf, whose partner gave birth to a baby girl in May, said: “Taking wee break from twitter. Every day a relentless barrage of abuse – mainly from same quarters.
“I’m thick-skinned politician but not going to sit back and just accept every time I turn my phone on, esp when my wee girl becomes the target.”
The Glasgow Pollok MSP said he still intended to keep using Instagram as he found it a “much nicer place”.
Speaking last year about racist and Islamophobic abuse on social media, Mr Yousaf said: “I get it every week and some of it can be very, very violent in terms of its manifestation.
“I get worried about my family. I’ve had a private briefing from police on the back of reporting some incidents. They said these are the steps you might want to take to protect your constituency office and so forth. It’s not a place you want to be in – but I’ve had to take those steps.
“I carry a personal alarm. I just do that as par for the course and carry it in my jacket. I shouldn’t have a need to carry it.”
In 2015, Johnathan McAuley, from Huddersfield, was fined £500 at Airdrie Sheriff Court after sending a racist message to Mr Yousaf on Twitter. It came after Mr Yousaf published a message on the social media site on 12 March describing the BBC’s coverage of Jeremy Clarkson as “navel-gazing”.
A reply from McAuley’s Twitter account referred to the politician in derogatory terms, adding: “Don’t tell us white guys what we can and can’t do.”