In the northwestern Pakistani town of Hangu, at least 31 people died and up to 50 were wounded in a suicide bombing on a procession and in ensuing violence.
Local police said about 20 people died in the initial attack and in armed clashes.
In a separate attack, unidentified gunmen opened fire on a bus outside the town, killing four passengers, one of them a woman.
Four truck drivers were shot dead after a mob set fire to their vehicles.
While authorities have moved to quell the unrest, sending army and paramilitary forces into the area and broadcasting announcements calling for calm from mosques, there are reports that the situation remains "very bad".
Witnesses have reported hearing continued gunfire in the town, hours after the first incident, according to an AFP report.
"We have reports that some bodies are still lying in the streets and because of the violence and bad security situation they cannot be removed," said Hangu mayor Ghaniur Rehman.
In neighbouring Afghanistan, at least four people were killed and more than 90 injured in the western town of Herat in fierce clashes between hundreds of Sunnis and Shiites.
Two mosques and several vehicles were torched, and men attacked each other with stones and large sticks.
Hundreds of troops were rushed to the scene of the clashes, which were reportedly sparked by an exchange of insults.
There have been reports of hand grenades thrown and hand-to-hand fighting and stabbings.
About 500 troops were deployed to Herat, and officials said the situation has been brought under control.
Ashura, the holiest day of the year for the religious minority, marks the end of ten days of mourning for the death of Imam Hussein, the Prophet Mohammed's grandson, in the seventh century.
Many Shiites mark the ceremony by publicly wailing and flagellating themselves with knives attached to chains.
Militants linked to Sunni Muslims are suspected of the Pakistan attack, which comes as Muslim sentiment around the world continues to boil, with widespread demonstrations against the publication of cartoons of the Prophet Mohammed in European media.
Afghanistan is particularly tense after days of protests.
Ashura parades have in the past often been subject to attacks by Sunnis.
In 2004, 170 people were killed in attacks in Baghdad and Karbala, and another 44 died in a single incident last year.
Meanwhile, more than a million Shiites in Iraq marked Ashura in Karbala amid heavy security.
Large groups of men with their heads shaved marched towards Imam Hussein's mausoleum, flagellating their heads with knives and swords, many of them bleeding profusely.
Around 8,000 Iraqi security forces are in Karbala to prevent stampedes and attacks, earlier imposing a massive lockdown on the city.
Ashura was outlawed under the Sunni-dominated regime of Saddam Hussein.