The Argentina international midfielder will join on an initial one-year loan deal, with an option to buy the player permanently at the end of the season.
The fee for his permanent sale is expected to be €60 million (£55m/$67m), Goal can confirm.
“We are delighted to announce that we have reached agreement for the season-long loan signing of Giovani Lo Celso from Real Betis with an option to make the transfer permanent,” said a Tottenham statement.
He spent 2018-19 on loan at Betis where he impressed, scoring 16 goals in 45 appearances in all competitions.
That good form saw the Primera Division side make his temporary deal a permanent one, paying PSG €25m (£23m/$28m) for his services.
“The club wishes Giovani Lo Celso the best of luck in this transfer period,” Betis said on their official website.
The attacking midfielder started his career at Rosario in his home country, before Ligue 1 giants PSG snapped him up in the summer of 2016, immediately loaning him back to the Argentine club.
After his arrival in Paris, the 19-cap international helped the club win Ligue 1 in 2018, two Coupe de France titles and the 2018 Coupe de La Ligue. He made a total of 54 appearances in France, scoring six times.
Lo Celso joins Ryan Sessegnon, Tanguy Ndombele and Jack Clarke as new faces in north London.
The 18-year-old Clarke has been loaned back to Leeds United for this season.
Spurs famously did not make any signings last season, with Lucas Moura the last player to join the club, in January 2018, before the arrivals of Ndombele and Clarke.
There were links to Paulo Dybala this week, but that move has fallen through, but they were able to get Lo Celso over the line just after the transfer window shut on Thursday.