Johnson campaigned successfully for Britons to vote to leave the European Union last month. In France, a founding EU member, he is seen as a key player in the departure and in the setback to European integration it represents.
"I am not at all worried about Boris Johnson, but... during the campaign he lied a lot to the British people and now it is he who has his back against the wall," said Ayrault on Europe 1 radio.
After the vote on June 23, Johnson turned his back on a chance to stand as prime minister in place of Conservative David Cameron, who stepped down having led the campaign to stay.
However, on Wednesday, Cameron's successor, Theresa May, appointed the former mayor of London and one-time journalist as her foreign secretary.
Johnson will not be in charge of talks about how the divorce will be arranged. May named David Davis, a pro-Brexit former Conservative Party chairman, to a special ministerial role for that purpose.
Nevertheless, the normally soft-spoken former French prime minister Ayrault had a strong warning for the new foreign policy chief of his near neighbor.
"(He has) his back against the wall to defend his country but also with his back against the wall the relationship with Europe should be clear," Ayrault said.
"I need a partner with whom I can negotiate and who is clear, credible and reliable," he added.
"We cannot let this ambiguous, blurred situation drag on... in the interests of the British themselves."
France and other EU partners have urged Britain to trigger quickly the process of exiting the bloc so that a two-year period of talks about trade terms and other links can begin. May has indicated she does not intend to do that this year.