The Paris Saint-Germain star came on at half-time and blasted home in front of the Kop with 69 minutes gone, four years on from his double against the same opponents at the 2014 World Cup, before Roberto Firmino added a late second.
Neymar's strike was a rare moment of quality in a match in which both sets of players seemed eager to keep injury risks to a minimum, with less than two weeks to go until the start of this year's World Cup finals.
Brazil head to Russia as one of the favourites but this was a largely flat display, despite Tite choosing to start Gabriel Jesus, Willian and Philippe Coutinho, making his first appearance at the stadium since leaving Liverpool for Barcelona in January.
Indeed, Croatia had arguably the better of the chances before Neymar produced his moment of magic, collecting Coutinho's pass and dancing into space before finishing from close range in his first appearance since surgery on a broken foot.
23 - For his return from injury, Neymar has scored only 23 minutes & 33 seconds after coming off the bench with Brazil v Croatia. Playstation. pic.twitter.com/W2U1oAbBD1— OptaJean (@OptaJean) June 3, 2018
Brazil, in their first visit to Merseyside since 1995, started on the front foot but almost fell behind 14 minutes in when Liverpool's Dejan Lovren headed a corner inches wide.
Andrej Kramaric caught Thiago Silva with a careless high foot and almost capitalised on the centre-back's struggle to shake off the knock, robbing him of possession before shooting straight at Alisson.
There were three bookings in a surprisingly feisty first half and Neymar's first involvement off the bench saw him side-step a potentially painful lunge from Lovren, who was trying to halt his run.
Brazil were finding it hard to fashion chances despite having close to 69 per cent of the ball, with Alisson again forced into action to parry Ante Rebic's header, as both coaches took the opportunity to make further changes to their sides.
That was until Tite's men suddenly exploded into life 69 minutes in. Willian found Coutinho in space, he slid the ball to Neymar and the PSG man did the rest, facing up to Sime Vrsaljko before cutting onto his right foot and blasting high into the net.
Coutinho earned a warm reception from the Anfield crowd as he was replaced late on by Fred, who has been tipped to complete a move to Manchester United in the coming days.
It was a current Liverpool hero who sealed a stylish end to the match, though, Firmino chesting down Casemiro's flighted pass before lifting a neat finish over Danijel Subasic with practically the last kick of the game.