The world's top ranked doubles team, the pair started playing together in 2015 and won their first three tournaments before capturing the 2015 Wimbledon and US Open titles as well as this year's Australian Open.
But their 41-match win streak ended in Qatar this year and they were defeated in the fourth round at Roland Garros and Wimbledon quarterfinals.
"After three Grand Slam victories and 11 WTA doubles titles together, we have mutually agreed that we would be open to playing with other players for the remainder of the season," Hingis and Mirza wrote in a joint statement posted on Twitter.
"Perhaps, because of our great results, we have had very high expectations and unfortunately did not get the results we desired recently.
"We would like to clarify that it was a totally professional decision based purely on our recent results."
It is understood that Hingis will now play with Coco Vandeweghe of the United States while Mirza joins up with Barbora Strycova of the Czech Republic for the remainder of the regular season.
"The professional decision has not and will not in any way affect the wonderful personal relationship that we continue to share," they added.
"We also look forward to defending our title in the year-end WTA Finals in Singapore in October for which 'Santina' (their combined nickname) has already qualified."
Hingis is playing with Swiss compatriot Timea Bacsinszky in Rio; the pair play their quarterfinal match later on Thursday.