The company's board of directors announced Saikawa's departure, which is effective September 16, after a meeting on Monday. It named Chief Operating Officer Yasuhiro Yamauchi as acting CEO while Nissan searches for a successor.
Saikawa's resignation came just days after he admitted to reporters in Japan that he and other top Nissan executives were overpaid as part of a stock-related payment plan. He denied any wrongdoing, and said he would return excess funds.
The Nissan board also revealed that an investigation found that alleged misconduct by former chairman Ghosn and Greg Kelly, a former Nissan director, cost the company billions in damages. It identified payments, some of which were deferred and never made, worth roughly 35 billion yen ($327 million). Nissan Board Chairman Yasushi Kimura said the company would not disclose further details because of ongoing judicial proceedings.
Details about the payments to Saikawa emerged in news reports ahead of Monday's board meeting. Speaking to reporters at a press conference in Japan on Monday, Kimura said the company's stock appreciation rights program, or SAR, was a subject of the probe triggered by Ghosn's surprise arrest.
While the payments to Saikawa were not illegal, the program was "intentionally manipulated" to increase the amount of money that could be gained from it, Kimura said.
"As a governance issue, we take it seriously," he added.
Kimura did not say that Saikawa's resignation was directly linked to any excess pay he received. Instead, the CEO had for some time intended to "hand the baton" to a successor and the company was ready to move on, he added.
Even before Saikawa's compensation came under scrutiny, his leadership of Nissan was in doubt. A lackluster earnings reports in May — when Saikawa said Nissan had hit "rock bottom" — prompted questions about whether the 65-year-old executive could survive. Profits have plummeted, and Nissan said in July that it will slash roughly 12,500 jobs from its workforce worldwide.
Speaking to reporters Monday, Saikawa reiterated that he decided to return money he said he "shouldn't have received."
Ghosn's downfall created a crisis for the company. Nissan's alliance with Renault and Mitsubishi has been thrown into turmoil, and questions over the company's reporting of executive pay have continued to surface.
Ghosn is now under house arrest in Tokyo, where he faces charges of financial misconduct, as well as allegations that he understated his income for years and abused his position by transferring personal investment losses to Nissan. He denies the charges against him, claiming that fears over a merger prompted a revolt at Nissan and led to his ouster.
Correction: An earlier version of this story incorrectly attributed the 35 billion yen cost to the investigation rather than the alleged misconduct.
CNN's Yoko Wakatsuki in Tokyo contributed to this report.