The American world record holder over 400m hurdles and fastest in the world this year over the flat had planned to race the latter event in Budapest but withdrew two weeks ago due to a knee problem.
With Olympic and defending world champion Shaunae Miller-Uibo only seventh in her heat four months after having a baby, Paulino has a great opportunity to claim her first individual global gold.
She was silver medallist last year and at the Tokyo Olympics, is the second-fastest in the field this season, and won the final heat easily in 49.90, the only sub-50 second time on a blazingly hot morning.
Poland's Natalia Kaczmarek, Cynthia Bolinga of Belgium and Jamaican Candice McLeod were not far behind as all three qualified from a fast opening heat.
Sada Williams of Barbados, the bronze medallist last year and the Commonwealth champion, also looked sharp before slowing almost to a walk in winning her heat.
In the men's event, 20-year-old Norwegian Havard Bentdal Ingvaldsen looked utterly bemused as he crossed the line in 44. 39 seconds, breaking his own national record and qualifying fastest.
Ingvaldsen held his arms out in confusion as his time came up on the big screen before breaking into a beaming smile.
Former Olympic and double world champion Wayde Van Niekerk of South Africa looked to be back towards his best form after a long injury absence, running an impressive 44.57.
The world record holder is likely to be duelling for gold with Tokyo Olympic champion and 2019 world champion Steven Gardiner of the Bahamas, the fastest in the world this year, who also looked comfortable running 44.65.
The semi-finals of the women's event are on Monday with the final on Wednesday, while the men's semis are on Tuesday with a Thursday evening final.
