Exporting live animals for slaughter and fattening will be banned under new plans.
A government consultation has been launched aimed at ending the practice in England and Wales, which officials said could not be stopped while the UK was part of the EU.
Reducing maximum journey times, giving animals more space and headroom during transport and stricter rules on transporting livestock in extreme temperatures and by sea are also proposed.
Around 6,400 animals were transported for slaughter in 2018, officials said, just a tiny fraction of the millions of UK beasts killed for human consumption every year.
Ministers are keen to make good on a promise that Brexit would allow the UK to prevent unnecessary suffering of animals during transport on excessively long journeys.
The eight-week consultation, launched on Wednesday, marks "a major step forward in delivering on our manifesto commitment to end live exports for slaughter," Environment Secretary George Eustice said.
"Now that we have left the EU, we have an opportunity to end this unnecessary practice. We want to ensure that animals are spared stress prior to slaughter," he added.
Chris Sherwood, the RSPCA's chief executive, said: "There is absolutely no reasonable justification to subject an animal to an unnecessarily stressful journey abroad simply for them to be fattened for slaughter.
"Ending live exports for slaughter and further fattening would be a landmark achievement for animal welfare."
Peter Stevenson, Compassion in World Farming's chief policy adviser, said the "unambiguous proposal" was very welcome.
"We urge farmers not to oppose the proposed ban but rather to recognise that this is an important part of moving forward to a high welfare future."
Lindsay Duncan, World Animal Protection's farming campaigns manager, said: "Live animal exports are cruel and unnecessary.
"Instead of subjecting animals to suffering on long, distressing journeys in cramped conditions, we believe live exports, and indeed any imports of live animals, should end.
"This landmark move for animal welfare will prevent suffering on an enormous scale."
MPs have warned of a "risk of serious disruption and delay" at Channel crossings when the Brexit transition period expires at the end of the month.
The UK and EU have not yet agreed their future trading relationship and further talks are planned this week.