A NASA TV broadcast showed the Russian Soyuz capsule carrying USA astronaut Jack Fischer, 43, and Russian cosmonaut Fyodor Yurchikhin, 58, lifting off at 1:13 p.m. local time/3:13 a.m. EDT (0713 GMT), "with a rare empty third seat".
The other notable aspect of Thursday's launch is the size of the crew-two rather than three.
In an emotional interview with NASA TV, Fischer, a 43- year-old former United States air force pilot, said he would be "thinking about Dad" as he enters orbit.
The arrival of Fischer and Yurchikhin increased the station's crew complement to five.
Roscosmos also unveiled the emblem for expedition 51, which Yurchikhin said was inspired by the US' second moon mission, Apollo-12.
"It's so lovely", US astronaut Jack Fischer described today's trip to the ISS to his wife.
The crew's unofficial patch - or rather, patches - directly mimic the two designs of the USA and Russian insignia for the Apollo-Soyuz Test Project.More news: Moneysupermarket.Com Group PLC (MONY) Receives "Hold" Rating from Liberum Capital
Another Russian-American duo, Yuri Malenchenko and Edward Lu, undertook the last two-man mission to the ISS, in April 2003.
Whitson, who on Monday (April 24) will surpass the record for the most time spent in space by an American astronaut - 534 days and counting, in the course of her three flights - recently had her own stay extended. Created with the assistance of Houston-based artist Blake Dumesnil, the primary patch keeps the general placement and look of the Soyuz on the Robert McCall-derived 1975 patch, but replaces the Apollo spacecraft with the International Space Station.
About six hours later, they docked at the orbiting outpost.
Fischer, a first-time space flier, and Yurchikhin, a veteran of four spaceflights, will spend more than 4 months aboard the orbiting laboratory before returning to Earth in early September.
US President Donald Trump and daughter Ivanka Trump are expected to congratulate Whitson on her achievement in an Earth-to space call on Monday, according to NASA.
Novitskiy and Pesquet will return to Earth on June 2 and Yurchikhin will take over as commander of Expedition 52. By reducing the number of its crew members, Russia will need to fly fewer Progress cargo ships, which deliver food and supplies to the Russian side of the station.
Soyuz MS-04 official mission patch.