A medical fluid machine with supply autoconnection, the machine comprising: a cassette-receiving wall; a disposable cassette held firmly by the wall, the disposable cassette including a port spike, the port spike fitted with a spike cap; a translating shuttle including a channel sized to hold a portion of a supply tube and including a fixture for releasably holding a supply tube end; a supply tube including an end configured to be releasably held by the fixture of the channel of the translating shuttle, the supply tube fitted with a supply tube cap; a cap removal device selectively positionable between the disposable cassette and the translating shuttle; and a controller programmed to (i) translate the shuttle holding the supply tube at the supply tube end towards the disposable cassette, so that the cap removal device is likewise moved towards the disposable cassette and the spike cap of the disposable cassette is engaged, (ii) translate the shuttle holding the supply tube at the supply tube end away from the disposable cassette and the cap removal device, so that the cap removal device can pull the spike cap off of the port spike and the tube cap off of the tube end, and (iii) translate the shuttle back towards the disposable cassette to allow the port spike of the cassette to spike the tube end.