Djokovic was stung by a third-round hammering by France's Jo-Wilfried Tsonga, who got past the Serb in less than an hour en route to taking the ATP Masters title in Toronto on Sunday.
Williams fell in the semi-finals of the WTA's sister tournament in Montreal, losing to her elder sister Venus for the first time since 2009.
She'll be eager to get back on track before heading to the US Open, which starts on August 25 and will be her last chance this year to add to her cache of 17 major titles.
Djokovic has some major repair work looming after being frustratingly crushed by Tsonga.
The newly-married Serb, who has never won a Cincinnati title despite four trips to the final, may benefit from the continuing injury absence of Rafael Nadal.
The 2013 Cincinnati champion from Spain is racing the clock to recover from a right wrist injury in time to defend his title at the year's last Grand Slam.
But Djokovic acknowledged that the loss to Tsonga was a bewildering blow to the confidence he'd gained with a Wimbledon title in July.
"Confidence is the hardest thing to get but easiest thing to lose," said Djokovic, who has the added incentive in Cincinnati of having never won the title, despite four trips to the final.
"Hopefully I can go one step further this time, but I haven’t been playing as well as I wanted in Toronto," he said. "So these couple of days I've put a lot of hours in on the practice court to upgrade my game and get my level of performance where it needs to be in order to have a chance to go far in the tournament."
Roger Federer, who fell to Djokovic in five sets in the Wimbledon final, was Tsonga's final victim in Toronto, falling in the championship match 7-5, 7-6 (7/3).
In Cincinnati the Swiss great will be returning to a tournament he has won five times, most recently in 2012.
- Federer 'here to win' -
Less than a week after turning 33, the Swiss, second seed behind Djokovic, is playing the tennis of a man a decade younger.
"I just keep on going," said the 17-time Grand Slam champion, who has won titles in Dubai and Halle this year. "Clearly I'm not here to just be here, to show up and soak it up and enjoy it and do press.
"I'm not coming for that," Federer said. "I'm really here to try to win."
Swiss Stan Wawrinka, who broke through for his first Grand Slam title at the Australian Open, is seeded third and he, too, will be seeking to rebound after exiting in Toronto in the third round.Czech Tomas Berdych is seeded fourth, ahead of Canadian Milos Raonic and Spain's number six David Ferrer.
Toronto semi-finalist Grigor Dimitrov is seeded seventh ahead of two-time Cincinnati winner Andy Murray, who is without new coach Amelie Maresmo this week as part of a pre-planned break.
"I need to stop losing matches that I'm leading," said Murray, whose last title was his 2013 Wimbledon triumph 13 months ago.
On the women's side, double Wimbledon winner Petra Kvitova is seeded second behind Williams, with Montreal champion Agnieszka Radwanska third.
Maria Sharapova, seeded fourth, and Wimbledon finalist and fifth seed Euenie Bouchard both have ground to make up after early exits in Montreal.