Henry was a good man for the king to have on his side, but Richard II did not seem to appreciate this. In 1398 Richard delighted in banishing Henry into exile on the grounds of past treasonable acts. The banishment was originally for ten years. In February 1399 Henry succeeded his father as Duke of Lancaster. King Richard chose to deprive Henry of his estates and extend the sentence to life. Henry invaded England in July and within six weeks Richard submitted to him. Henry succeeded in convincing Parliament of his eligibility to the throne (Edmund Mortimer, earl of March, had a prior claim, but he was only seven years old). Nevertheless it was an uneasy succession. For all that nearly everyone welcomed Henry over Richard, those who had supported Richard became concerned for their own lives and estates. Within months of his succession Henry found his life threatened in a rebellion organized by the earls of Kent, Salisbury and Huntingdon. Henry's retribution upon the earls and their supporters was swift and violent. It is likely that in its aftermath Henry also ordered the murder of the king who was starved to death, though the guilt of this continued to haunt Henry for the rest of his life.

Within a few months Henry faced a further revolt, this time in Wales, where Owain Glyn Dwr was declared prince in September 1400. Although the initial revolt was swiftly put down by Henry, Owain was not caught and several years of guerilla warfare followed. Support for Owain grew, not only amongst the Welsh, but amongst the English barons who had their own axes to grind. Key amongst these were the marcher lords, the Mortimers, who believed that their heir, Edmund, was the rightful king of England. This heir's uncle, also called Edmund, was won over to the Welsh cause and married Glyn Dwr's daughter. Owain also found support from Henry Percy, the son of the earl of Northumberland. Young Percy, better known as Hotspur, was a vain and intolerant individual who never believed he had received just recognition for his border successes against the Scots. Moreover his wife was Mortimer's sister. In 1403 Hotspur threw in his lot with Glyn Dwr and Mortimer. Henry reacted quickly, before Hotspur and Mortimer could combine forces, and confronted Hotspur at the battle of Shrewsbury on 21 July 1403. Hotspur was killed and his uncle, the earl of Worcester, was captured and executed. Hotspur's father, Henry, earl of Northumberland, was spared, but he continued to plot against the king. By 1405 it became evident that Mortimer and Percy were planning to overthrow Henry and share England between them. Both Thomas Mowbray, the Earl Marshal of England, and Richard Scrope, archbishop of York, became involved in the plot. The rebel army was defeated and this time Henry showed no mercy, though there was a great outcry when the archbishop was executed. Although the earl of Northumberland escaped to Scotland, he died in February 1408. Soon after Edmund Mortimer died during the siege of Harlech and the Welsh rebellion faded away.

At last by 1408 Henry felt reasonably safe. Two years earlier he had taken James I of Scotland captive when the young heir to the throne was being sent to France for safety. James remained at the court of the English king for the next seventeen years and, with him as hostage, England's relationship with Scotland remained stable. More over threats from France diminished as the French became riven by its own civil war. Unfortunately for Henry his physical constitution gave way and for several years, between 1406 and 1409, there were concerns for his life. In addition to the stress of keeping his throne amid widespread opposition, Henry had struggled to sustain the administration and finance of England. Henry placed considerable demands upon his treasury, and Parliament often argued against him. Henry remained moderate throughout, careful to avoid a confrontation that might cost him his throne. He relied increasingly on his council to help him run his government. However, it became evident that his illness was taking its toll and that Henry was finding it difficult to govern. By 1409 his son, Prince Henry, was made chancellor in place of the king's favoured Thomas Arundel, archbishop of Canterbury. Arundel returned in 1411 amidst a quarrel between the King and his council, in which it seems it had been proposed that Henry abdicate in favour of his son. Henry refused. Rumours abounded that Prince Henry was going to take the throne by force, but that never happened. He had little time to wait. Henry's strange wasting disease took his life in March 1413, two weeks before his forty-sixth birthday. The valiant knight of twenty years earlier had been worn out by the stress of government and ill health. Nevertheless he had established a united kingdom, and passed on the throne to his son, Henry V, who would become one of England's best-known kings.

Henry had desired that he be buried at Canterbury Cathedral rather than Westminster Abbey. There is a story that while a ship bore his coffin down the Thames a storm erupted and the king's body was washed overboard. The sailors later substituted another body. When Henry's tomb at Canterbury was opened in 1832, the simplicity of the remains suggested that the story may have been true.